Eleven genetic markers were typed in 112 unrelated patients with migraine (50 with aura, 62 without aura) and compared with a random sample of healthy individuals. No significant differences were found for the ABO and Rh systems, acid phosphatase 1, phosphoglucomutase 1, adenosine deaminase, haptoglobin, transferrin, alpha-1-antitrypsin, and D1S80. Strong associations between the group of patients with migraine and group-specific component GC 1F-1F and esterase-D ESD 2-2 phenotypes were observed. These associations raise the possibility that a molecular genetic factor for migraine may exist in or near the Group Component (chromosome 4) and Esterase D (chromosome 13) loci, and represent a first comprehensive step in the eventual localization and isolation of the migraine genes.